Keeping you up-to-date on recent headlines in neurology.
Sigma-Aldrich labs to work on genetic causes of Parkinson's ... Sigma-Aldrich (St. Louis) and The Michael J. Fox Foundation (MJFF; New York) reported a collaboration that is expected to develop more accurate preclinical research models of Parkinson's disease (PD), a neurodegenerative disorder of unknown cause that affects nearly five million individuals worldwide. Under a research grant from MJFF, Sigma Advanced Genetic Engineering (SAGE) Labs – an initiative of Sigma-Aldrich's Research Biotech business unit – will use novel CompoZr zinc finger nuclease (ZFN) technology in an effort to create superior preclinical research models critically needed for the development of transformative treatments for PD. The models, which are expected to take as little as one year to develop, will be made broadly accessible to scientists throughout the Parkinson's research community in order to speed basic research and drug development efforts field-wide. Research already conducted into the genetic causes of PD has identified a number of genes but indicates a strong connection to mutations in five particular genes: LRRK2, alpha-synuclein, DJ-1, Parkin and PINK1. MJFF funding will allow Sigma-Aldrich's efforts to create five novel rat models with each of these genes knocked out.
Key mechanism studied in the development of nerve cells ... Chaos brews in the brains of newborns: the nerve cells are still bound only loosely to each other. Under the leadership of Academy Research Fellow Sari Lauri, a team of researchers at the University of Helsinki has been studying for years how a neural network capable of processing information effectively is created out of chaos. The team has now found a new kind of mechanism that adjusts the functional development of nerve cell contacts. The results were published in the September issue of the Journal of Neuroscience. The work carried out by Lauri's team sheds light on a development path that results in some of the large number of early synapses becoming stronger. The researchers found out hat the BDNF growth factor of nerve cells triggers a functional chain which promotes the release of the neurotransmitter glutamate. BDNF enables the release of glutamate by prohibiting the function of kainate receptors which slow down the development of the preforms of the synapses. The activity of the kainate receptors restricts the release of glutamate and the development of synapses into functional nerve cell contacts. It is noteworthy that the brain of a newborn itself seems to organize its own development. The electrical activity of the waking brain triggers the series of events controlled by the BDNF protein, as a result of which kainate receptor activity disappears in some synapses.
Multiple strokes, not underlying vascular risk factors, increase risk of post-stroke dementia ... Multiple strokes and the complications and characteristics of the stroke itself are more important predictors of post-stroke dementia than are underlying vascular risk factors. As such, providing the best possible stroke care and secondary prevention measures could reduce the burden of dementia. These are the conclusions of an article published online in the November edition of The Lancet Neurology. Although it is widely accepted that stroke is associated with an increased risk of subsequent dementia, studies show conflicting results on the risk factors for and prevalence of pre-stroke and post-stroke dementia. Reliable data on the risks and predictors of post-stroke dementia are needed to inform patients and caretakers, plan clinical services and trials, and establish the overall burden of stroke, and to understand better the causes of post-stroke dementia. To provide more evidence, Sarah Pendlebury and Peter Rothwell from the Stroke Prevention Research Unit (Oxford, UK), conducted a systematic review of studies published between 1950 and May 1, 2009, to assess the conflicting prevalence data and to identify the risk factors for pre-stroke and post-stroke dementia. The authors found that the risk of dementia was associated with the occurrence of strokes and the number of strokes rather than with underlying vascular risk factors. Indeed, dementia rates were about three times as high after recurrent stroke than after first stroke. About 10% of patients developed dementia within the first few months of a first stroke and 30% of patients developed dementia after a recurrent stroke.
Fear, brain waves, and PTSD ... The brain is a complex system made of billions of neurons and thousands of connections that relate to every human feeling, including one of the strongest emotions, fear. Most neurological fear studies have been rooted in fear-conditioning experiments. Now, University of Missouri (Columbia) researchers have started using computational models of the brain, making it easier to study the brain's connections. Guoshi Li, an electrical and computer engineering doctoral student, has discovered new evidence on how the brain reacts to fear, including important findings that could help victims of post-traumatic stress disorder (PTSD). "Computational models make it much easier to study the brain because they can effectively integrate different types of information related to a problem into a computational framework and analyze possible neural mechanisms from a systems perspective. We simulate activity and test a variety of "what if" scenarios without having to use human subjects in a rapid and inexpensive way," Li said. From previous experiments, scientists have found that fear can subside when overcome with fear extinction memory, but it is not permanently lost. Fear extinction is a process in which a conditioned response to a stimulant that produces fear gradually diminishes over time as subjects, such as rats in auditory fear experiments, learn to disassociate a response from a stimulus. One theory has concluded that fear extinction memory deletes fear memory, and another concluded that fear memory is not lost, but is inhibited by extinction memory as fear can recover with the passage of time after extinction.
Prognostic factor shows chemotherapy alone just as effective as radiation ... Initial chemotherapy alone after surgery is just as successful as initial radiation therapy for patients from whom a very malignant brain tumor (anaplastic glioma) was removed. With this treatment, the patients survive on average > 30 months without a recurrence. A study conducted by the Neurooncology Working Group of the German Cancer Society (Heidelberg) showed that patients in primary therapy benefit to the same extent from chemotherapy alone as from radiation alone. The results of the study were published in the Journal of Clinical Oncology. In Germany, around 4,500 people a year develop a glioma, a malignant brain tumor. Some 5% of primary brain tumors are what are known as anaplastic gliomas. They respond to treatment somewhat better than most other malignant brain tumors. The mean survival time in the study was greater than 80 months. As the tumors can branch out widely into the surrounding tissue, they cannot be completely removed. The subsequent therapy in the form of combined radiochemotherapy (radiation and chemotherapy) is the current standard treatment, but it is associated with a risk of long-term toxicity to healthy brain tissue, causing the patient to lose cognitive abilities.
— Compiled by Rob Kimball, MDD